Abstract
BackgroundEarlier, we reported a highly statistically significant association between T-helper 1 (Th1) and Th2 cytokine genotypes and hepatocellular carcinoma (HCC) risk among natives of southern Guangxi, China, a hyperendemic region for HCC. Epidermal growth factor (EGF) plays a critical role in malignant transformation of hepatocytes and tumor progression. A polymorphism in the EGF gene (61A > G) results in elevation of EGF in liver tissues and blood. Epidemiological data are sparse on the possible association between EGF genetic polymorphism and HCC risk.MethodsThe EGF 61A > G polymorphism, multiple Th1 and Th2 genotypes, and environmental risk factors for HCC were determined on 117 HCC cases and 225 healthy control subjects among non-Asians of Los Angeles County, California, a low-risk population for HCC, and 250 HCC cases and 245 controls of southern Guangxi, China.ResultsFollowing adjustment for all known or suspected HCC risk factors, non-Asians in Los Angeles who possessed at least one copy of the high activity 61*G allele of the EGF gene showed a statistically non-significant, 78% increased risk of HCC compared with those possessing the EGF A/A genotype. This EGF-HCC risk association significantly strengthened among heavy users of alcohol [odds ratio (OR) = 3.44, 95% confidence interval (CI) = 0.93–12.76, P = 0.065)], and among individuals carrying the high-risk Th1/Th2 genotypes for HCC (OR = 3.34, 95% CI = 1.24-9.03, P = 0.017). No association between EGF genotype and HCC risk was observed among Chinese in southern Guangxi, China.ConclusionGenetic polymorphism in the EGF gene resulting in elevated level of EGF, may contribute to HCC risk among low-risk non-Asians in Los Angeles.
Highlights
Earlier, we reported a highly statistically significant association between T-helper 1 (Th1) and T-helper 2 (Th2) cytokine genotypes and hepatocellular carcinoma (HCC) risk among natives of southern Guangxi, China, a hyperendemic region for HCC
We examined the Epidermal growth factor (EGF) genotype – HCC risk association across different risk strata defined by genetic profiles (Th1/Th2 cytokine genotypes) or environmental exposures within each of the two study populations
We examined whether the EGF – HCC risk association differed across different risk profiles as determined by environmental exposures or the Th1/Th2 genotypes
Summary
We reported a highly statistically significant association between T-helper 1 (Th1) and Th2 cytokine genotypes and hepatocellular carcinoma (HCC) risk among natives of southern Guangxi, China, a hyperendemic region for HCC. China and Africa are areas of high HCC incidence where the primary cause of HCC is chronic infections with the hepatitis B virus (HBV), and dietary aflatoxin exposure being an important cofactor [2,3]. In low HCC incidence areas including Europe and North America, diverse environmental factors, including chronic HBV and hepatitis C virus (HCV) infections, heavy alcohol use, diabetes, obesity, and tobacco use have been shown to contribute to the local burden of HCC [3,4,5,6]. The inflammatory process persists over prolonged periods of time and the continual cell death/regeneration accompanying the process is recognized to enhance risk of cancer, including HCC (reviewed in [8]). The nodules can progress from a hyperplastic to a dysplastic phase and to HCC [7]
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